Submissions for variant NM_001083962.2(TCF4):c.1487-5G>A

gnomAD frequency: 0.00016  dbSNP: rs749176054

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Diagnostic Laboratory, Strasbourg University Hospital	RCV000224109	SCV000281738	uncertain significance	Intellectual disability	2014-07-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000298499	SCV000409527	benign	Pitt-Hopkins syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000422255	SCV000511826	likely benign	not provided	2016-08-04	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Genetic Services Laboratory, University of Chicago	RCV000503349	SCV000597420	uncertain significance	not specified	2015-09-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000298499	SCV000646112	likely benign	Pitt-Hopkins syndrome	2024-01-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000422255	SCV000976799	likely benign	not provided	2020-10-12	criteria provided, single submitter	clinical testing	In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect; Observed in an individual in published literature with intellectual disability; however, this individual did not have additional classic features of Pitt-Hopkins syndrome and segregation infomation was limited due to lack of a paternal sample (Redin et al., 2014); This variant is associated with the following publications: (PMID: 25167861)
Ambry Genetics	RCV002390593	SCV002701636	likely benign	Inborn genetic diseases	2021-05-05	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000422255	SCV005330256	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	TCF4: PP3, BS2
PreventionGenetics, part of Exact Sciences	RCV003955294	SCV004768649	likely benign	TCF4-related disorder	2023-07-25	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).